Background Gambling is illegal for children in Ghana. However, young people, including children, are increasingly engaged in gambling across the country. Gambling is harmful and poses developmental implications for the youth, including children. There are limited studies on child gambling in Ghana and other sub-Saharan African countries. This study examined the prevalence of gambling participation, predictors of gambling participation, and perceived harm of gambling on children. Methods A cross-sectional convergent parallel mixed methodology was used to study 5024 children aged 8 to 17 in the three ecological zones of Ghana. Binary logistic regression was used to examine the predictors of gambling participation while the qualitative data was analysed thematically. Results Overall, 3.1% of children aged 8 to 17 had ever engaged in gambling activities. Also, being a female (AOR = 0.210, Wald test = 34.413, 95% CI: 0.125–0.354), having attained primary education (AOR = 4.089, Wald test = 18.643, 95% CI: 2.158–7.749), doing paid work (AOR = 2.536, Wald test = 10.687, 95% CI: 1.452–4.430), having a friend who gambles (AOR = 1.587, Wald test = 4.343; 95% CI: 1.028–2.451), having access to radio (AOR = 1.658, Wald test = 6.694, 95% CI: 1.130–2.431) and having access to mobile phone (AOR = 0.590, Wald test = 6.737, 95% CI: 0.396–0.879) were predictors of gambling participation. Gambling is perceived as harmful by children since it is addictive, affects learning and class attendance, and makes them steal from their families to gamble. Conclusions This study demonstrated that socio-demographic characteristics (sex, age, educational attainment, ecological zone, persons taking care of children, living arrangement, engagement in paid work, radio access, mobile phone access) and gambling-related information (having friends who gamble) make children more susceptible to gambling. Researchers and policymakers should consider these socio-demographic characteristics and gambling-related information when designing interventions to curb gambling among children aged 8 to 17 in Ghana.